MiR-148a对氟伐他汀人体药代动力学特征的影响

Effect of miR-148a on the pharmacokinetic properties of fluvastatin in Chinese health subjects

目的研究人血浆中miR-148a的表达水平对人体内氟伐他汀药代动力学特征的影响。方法建立人血浆中氟伐他汀LC-MS/MS检测方法,比较miR-148a高表达组和低表达组间氟伐他汀人体药代动力学特征的差异。结果MiR-148a高表达组AUC_(0-12)、AUC_(0-∞)、C_(max)、V_(d)、CL分别为(775.61±136.59)ng·h·mL^(-1),(779.88±137.90)ng·h·mL^(-1),(727.56±150.61)ng·mL^(-1),(185.29±70.06)L,(52.81±9.92)L·h^(-1);miR-148a低表达组AUC_(0-12)、AUC_(0-∞)、C_(max)、V_(d)、CL分别为(520.53±122.11)ng·h·mL^(-1),(524.43±121.64)ng·h·mL^(-1),(457.86±103.56)ng·mL^(-1),(317.12±93.08)L,(79.48±16.25)L·h^(-1);miR-148a高表达组的AUC_(0-12)、AUC_(0-∞)、C_(max)明显高于低表达组,而CL、V_(d)低于低表达组。结论人血浆中miR-148a的表达水平与氟伐他汀药代动力学过程存在相关性。

Objective To investigate the effect of plasma miR-148a level on the pharmacokinetic properties of fluvastatin in Chinese health subjects.Methods To establish a method for the determination of fluvastatin in human plasma by LC-MS/MS.The human pharmacokinetic characteristics of fluvastatin were compared between the high expression group and the low expression group of miR-148a.Results The pharmacokinetic parameters AUC_(0-12),AUC_(0-∞),C_(max),V_(d) and CL of fluvastatin in miR-148a high expression group were(775.61±136.59)ng·h·mL^(-1),(779.88±137.90)ng·h·mL^(-1),(727.56±150.61)ng·mL^(-1),(185.29±70.06)L,(52.81±9.92)L·h^(-1).The pharmacokinetic parameters AUC_(0-12),AUC_(0-∞),C_(max),V_(d) and CL of fluvastatin in low expression group were(520.53±122.11)ng·h·mL^(-1),(524.43±121.64)ng·h·mL^(-1),(457.86±103.56)ng·mL^(-1),(317.12±93.08)L,(79.48±16.25)L·h^(-1).Compared with the miR-148a low-expression group AUC_(0-12),AUC_(0-∞),and C_(max) was significantly higher in the miR-148 a high-expression group but CL and V_(d)were lower in the miR-148 a high-expression group than the miR-148 a low-expression group.Conclusion The plasma miR-148a was related to the pharmacokinetics of fluvastatin in healthy Chinese subjects.